Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis.

Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis.
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发表时间:
2003-02
期刊:
影响因子:
11.2
通讯作者:
D. Reisman;J. Sciarrotta;Weidong Wang;W. Funkhouser;B. Weissman
D. Reisman;J. Sciarrotta;Weidong Wang;W. Funkhouser;B. Weissman
中科院分区:
医学1区
文献类型:
--
作者:
D. Reisman;J. Sciarrotta;Weidong Wang;W. Funkhouser;B. Weissman

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SWI/SNF复合体在肿瘤发生中的作用,基于其对视网膜母细胞瘤诱导的生长停滞和P53介导的转录以及SWI/SNF缺陷小鼠肿瘤的出现的需求。此外,Western印迹数据显示,在大约30%的人类非小细胞肺癌细胞系中,SWI/SNF ATPase亚单位细胞BRG1和BRM(BRG1/BRM)丢失。为了确定这些蛋白在原发肿瘤中是否存在表达缺失,我们用免疫组织化学方法检测了41例原发肺腺癌和19例原发肺鳞癌中这些蛋白的表达。这些分析表明,10%的肿瘤伴随着BRG1和BRM表达的丧失。此外,BRG1/BRM阴性的癌症患者,与BRG1/BRM患者相比,与BRG1/BRM患者相比,生存率显著降低,与分期无关。这份报告提供了BRG1和BRM作为肿瘤抑制蛋白的支持性证据,并暗示它们在非小细胞肺癌的发生发展中的作用。
A role for the SWI/SNF complex in tumorigenesis based on its requirement for retinoblastoma induced growth arrest and p53-mediated transcription and the appearance of tumors in SWI/SNF-deficient mice. In addition, Western blot data have shown that the SWI/SNF ATPase subunits cell, BRG1 and BRM (BRG1/BRM), are lost in approximately 30% of human non-small lung cancer cell lines. To determine whether loss of expression of these proteins occurs in primary tumors, we examined their expression in 41 primary lung adenocarcinomas and 19 primary lung squamous carcinomas by immunohistochemistry. These analyses showed that 10% of tumors show a concomitant loss of BRG1 and BRM expression. Moreover, patients with BRG1/BRM-negative carcinomas, independent of stage, have a statistically significant decrease in survival compared with patients with BRG1/BRM. This report provides supportive evidence that BRG1 and BRM act as tumor suppressor proteins and implicates a role for their loss in the development of non-small cell lung cancers.